A central problem in hematology, one with broad implications for inherited disorders and for leukemias, is how hematopoietic stem cells develop in the early embryo and how further differentiation of these cells is programmed. An understanding of the development of hematopoietic cells will require a interdisciplinary approach that combines classical developmental biology and contemporary genetics. Our goal is to organize a Center of Excellence in Hematology devoted to Molecular Developmental Hematopoiesis. Our plan rests on the underlying premise that maximum progress can be achieved by parallel study of hematopoietic development and specific genes critical to it in mouse, frog, and fish. As such, we envision a mouse gene targeting core under the direction of the PI, Dr. Stuart H. Orkin, a Xenopus developmental hematopoiesis core under the direction of Dr. Douglas A. Melton, and a Zebra fish core for the identification of new mutants in hematopoietic development under the direction of Dr. Leonard I. Zon. During the planning phase, we hope to identify and recruit a junior investigator in the area of gene transfer who will be able to bring the fundamental observations in developmental regulation to clinical application in the future. Affiliated Investigators in the Harvard Medical Area with a focus of interest on genes important for hematopoietic cell development will be able to expand their analyses in any of the above systems through interaction with the cores. These collaborations will increase awareness and focus in this important research area and provide a training ground for new investigators in the field. In the planning phase we seek to stimulate close interaction and discussions among researchers in the Harvard Medical area in the general field of hematopoiesis, design the appropriate framework and organization for the Center and its cores, identify the most relevant research projects for study at the inception of the Center, and identify a new recruit in the field of gene transfer.